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Non-Immunosuppressant Medication Use in Heart Transplant Patients: A Guide for Pharmacists

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DOI: 10.4236/pp.2014.510107    2,384 Downloads   2,785 Views  

ABSTRACT

For heart transplant patients, there are a number of non-immunosuppressant medications that are routinely prescribed to mitigate the side-effects of immunosuppression, treat the related complications, and improve long-term survival. This review focuses on the medications used to prevent and manage cardiac allograft vasculopathy (CAV), hypertension, dyslipidemia and osteoporosis. The rationale and evidence supporting their use are summarized and the immunosuppressant drugs are only discussed briefly, as they relate to each of these medical issues. Pharmacy practitioners are likely to encounter patients post-cardiac transplant in a variety of clinical settings; therefore, a concise appreciation of the principles for the long-term medical management of these patients is important when providing collaborative care.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Egan, G. and Pearson, G. (2014) Non-Immunosuppressant Medication Use in Heart Transplant Patients: A Guide for Pharmacists. Pharmacology & Pharmacy, 5, 950-958. doi: 10.4236/pp.2014.510107.

References

[1] Fischer, S. and Glas, K.E. (2013) A Review of Cardiac Transplantation. Anesthesiology Clinics, 31, 383-403.
http://dx.doi.org/10.1016/j.anclin.2013.01.003
[2] Deng, M.C. (2002) Cardiac Transplantation. Heart, 87, 177-184.
http://dx.doi.org/10.1136/heart.87.2.177
[3] Stehlik, J., Edwards, L.B., Kucheryavaya, A.Y., Aurora, P., Christie, J.D., Kirk, R., Dobbels, F., Rahmel, A.O. and Hertz, M.I. (2010) The Registry of the International Society for Heart and Lung Transplantation: Twenty-Seventh Official Adult Heart Transplant Report—2010. The Journal of Heart and Lung Transplantation, 29, 1089-1103.
http://dx.doi.org/10.1016/j.healun.2010.08.007
[4] Lindenfeld, J., Page, R.L., Zolty, R., Shaker, S.F., Levi, M., Lowes, B., Wolfel, E. and Miller, G.G. (2005) Drug Therapy in the Heart Transplant Recipient: Part III Common Medical Problems. Circulation, 111, 113-117.
http://dx.doi.org/10.1161/01.CIR.0000151609.60618.3C
[5] Thibodeau, J.T., Mishkin, J.D., Patel, I.C., Mammen, P., Warkham, D.W. and Drazner, M.H. (2012) IIIB or Not IIIb: A Previously Unanswered Question. Journal of Cardiac Failure, 18, 367-372.
http://dx.doi.org/10.1016/j.cardfail.2012.01.016
[6] Constanzo, M.R. and Burch, M. (2010) The International Society of Heart and Lung Transplantation Guidelines for the Care of Heart Transplant Recipients. The Journal of Heart and Lung Transplantation, 29, 914-956.
http://dx.doi.org/10.1016/j.healun.2010.05.034
[7] Haddad, H., Isaac, D., Lagare, J.F., Pfiugfelder, P., Hendry, P. and Chan, M. (2009) Canadian Cardiovascular Society Consensus Conference Update on Cardiac Transplantation 2008: Executive Summary. Canadian Journal of Cardiology, 25, 197-205.
http://dx.doi.org/10.1016/S0828-282X(09)70061-3
[8] Crespo-Leiro, M.G., Marzoa-Rivas, R., Barge-Caballero, E. and Pariagua-Martin, M.J. (2012) Prevention and Treatment of Coronary Artery Vasculopathy. Current Opinion in Organ Transplantation, 17, 546-550.
http://dx.doi.org/10.1097/MOT.0b013e3283577fd9
[9] Sanchez Lazaro, I.J., Bonet, L., Lopez, J.M., Lacueeta, S. and Martinez-Dolz, L.L. (2008) Influence of Traditional Cardiovascular Risk Factors in the Recipient on the Development of Cardiac Allograft Vasulopathy after Heart Transplantation. Transplantation Proceedings, 40, 3056-3057.
http://dx.doi.org/10.1016/j.transproceed.2008.08.115
[10] Tona, F., Perazzolo, M., Fedrigo, M., Famoso, G., Bellu, R., Thiene, G., Gerosa, G., Angelini, A. and Iliceto, S. (2012) Recent Development on Coronary Microvasculopathy after Heart Transplantation: A New Target in the Therapy of Cardiac Allograft Vasculopathy. Current Vascular Pharmacology, l10, 206-215.
http://dx.doi.org/10.2174/157016112799304987
[11] Valantine, H.A., Gao, S.Z., Menon, S.G., Renlund, D.G., Hunt, S.A., Oyer, P., Stinson, E.B., Brown, B.W., Merigan, T.C. and Schroeder, J.S. (1999) Impact of Prophylactic Immediate Posttransplant Ganciclovir on Development of Transplant Atherosclerosis: A Post Hoc Analysis of a Randomized, Placebo-Controlled Study. Circulation, 100, 61-66. http://dx.doi.org/10.1161/01.CIR.100.1.61
[12] Benza, R.L., Zoghbi, G.J., Tallaj, J., Brown, R., Kirklin, J.K., Hubbard, M., Rayburn, B., Foley, B., McGiffin, D.C., Pinderski, L.J., Misra, V. and Bourge, R.C. (2004) Palliation of Allograft Vasculopathy with Transluminal Angioplasty. Journal of the American College of Cardiology, 43, 1973-1981.
http://dx.doi.org/10.1016/j.jacc.2004.02.045
[13] Zhang, R., Haverich, A., Struber, M., Simon, A. and Bara, C. (2008) Delayed Onset of Cardiac Allograft Vasulopathy by Induction Therapy Using Anti-Thymocyte Globulin. The Journal of Heart and Lung Transplantation, 27, 603-609.
http://dx.doi.org/10.1016/j.healun.2008.02.016
[14] Bonaros, N., Dunkler, D., Kocher, A., Imhof, M., Grimm, M., Zuckermann, A., Wolner, E. and Laufer, G. (2006) Ten-Year Follow-Up of a Prospective, Randomized Trial of BT563/BB10 versus Anti-Thymocyte Globulin as Induction Therapy after Heart Transplantation. The Journal of Heart and Lung Transplantation, 25, 1154-1163.
http://dx.doi.org/10.1016/j.healun.2006.03.024
[15] Dandel, M. and Hetzer, R. (2010) Impact of Immunosuppressive Drugs on the Development of Cardiac Allograft Vasculopathy. Current Vascular Pharmacology, 8, 706-719.
http://dx.doi.org/10.2174/157016110792006923
[16] Guethoff, S., Meiser, B.M., Eifert, S., Grinninger, C., Ueberfuhr, P., Reichart, B., Hagl, C. and Kaczmarek, I. (2013) Ten-Year Results of a Randomized Trial Comparing Tacrolimus versus Cyclosporine A in Combination with Mycophenolate Mofetil after Heart Transplantation. Transplantation, 95, 629-634.
http://dx.doi.org/10.1097/TP.0b013e318277e378
[17] Topilsky, Y., Hasin, T., Raichlin, E., Boilson, B.A., Schirger, J.A., Pereira, N.L., Edwards, B.S. and Clavell, A.L. (2012) Sirolimus as Primary Immunosuppression Attenuates Allograft Vasculopathy with Improved Late Survival and Decreased Cardiac Events after Cardiac Transplantation. Circulation, 125, 708-720.
http://dx.doi.org/10.1161/CIRCULATIONAHA.111.040360
[18] Kaczmarek, I., Ertl, B., Schmauss, D., Sadoni, S., Knez, A., Daebritz, S., Meiser, B. and Reichart, B. (2006) Preventing Cardiac Allograft Vasculopathy: Long-Term Beneficial Effects of Mycophenolate Mofetil. The Journal of Heart and Lung Transplantation, 25, 550-556.
http://dx.doi.org/10.1016/j.healun.2006.01.003
[19] Arora, S., Ueland, T., Wennerblum, B. Sigurdadottir, V., Eiskjaer, H., Botker, H.E., Ekmehag, B., Jansson, K., Mortensen, S.A. and Saunamaki, K. (2011) Effect of Everolimus Introduction on Cardiac Allograft Vasculopathy—Results of a Randomized, Multicentre Trial. Transplantation, 92, 235-243.
http://dx.doi.org/10.1097/TP.0b013e31822057f1
[20] Hilbrands, L.B., Dernacker, P.N., Hoitsma, A.J., Stalenhoef, A.F. and Koene, R.A. (1995) The Effects of Cyclosporine and Prednisone on Serum Lipid and (Apo)lipoprotein Levels in Renal Transplant Recipients. Journal of the American Society of Nephrology, 5, 2073.
[21] Mehra, M.R., Ventura, H.O., Smart, F.W., Collins, T.J., Ramee, S.R. and Stapleton, D.D. (1995) An Intravascular Ultrasound Study of the Influence of Angiotensin-Converting Enzyme Inhibitors and Calcium Entry Blockers on the Development of Cardiac Allograft Vasculopathy. American Journal of Cardiology, 75, 853-854.
http://dx.doi.org/10.1016/S0002-9149(99)80432-9
[22] Pethig, K., Horing, B., Bara, C., Schieffer, B., Haverich, A. and Sachse, A. (2008) Eprosartan in the Primary Prevention of Cardiac Allograft Vascular Disease: A Double-Blind Prospectively Randomized Study Using Intravascular Ultrasound. Journal of International Medical Research, 36, 1022-1031.
http://dx.doi.org/10.1177/147323000803600520
[23] Yamamoto, T., Sata, M., Fukuda, D. and Takamoto, S. (2006) The Angiotensin II Type 1 Receptor Blocker Candesartan Attenuates Graft Vasculopathy. Journal of Surgical Research, 132, 62-68.
http://dx.doi.org/10.1016/j.jss.2005.07.011
[24] Grigioni, F., Potena, C.L., Fabbri, F., Russo, A., Muauraca, A.C., Coccolo, F. and Magnani, G. (2006) Long-Term Safety and Effectiveness of Statin for Heart Transplant Recipients in Routine Clinical Practice. Transplantation Proceedings, 38, 1507-1510.
http://dx.doi.org/10.1016/j.transproceed.2006.02.071
[25] Kobagashi, J.A., Moriguichi, J.D., Laks, H., Wener, L., Hage, A., Hamilton, M.A., Cogert, G., Marquez, A., Vasstlakis, M.E., Patel, J. and Yeatman, L. (2005) Ten-Year Follow-Up of a Randomized Trial of Pravastatin in Heart Transplant Patients. The Journal of Heart and Lung Transplantation, 24, 1736-1740.
http://dx.doi.org/10.1016/j.healun.2005.02.009
[26] Patel, D.N., Pagnani, F.D., Koelling, T.M., Dyke, D.B., Baliga, R.R., Cody, R.J., Lake, K.D. and Aaronson, K.D. (2002) Safety and Efficacy of Atorvastatin in Heart Transplant Recipients. The Journal of Heart and Lung Transplantation, 21, 204-210.
http://dx.doi.org/10.1016/S1053-2498(01)00369-2
[27] Mehra, M.R., Uber, P.A., Vivekananthan, K., Solis, S., Soctt, R.L., Park, M.H., Milani, R.V. and Lavie, C.J. (2002) Comparative Beneficial Effects of Simvastatin and Pravastatin on Cardiac Allograft Rejection and Survival. Journal of the American College of Cardiology, 40, 1609-1614.
http://dx.doi.org/10.1016/S0735-1097(02)02340-9
[28] Anderson, T.J., Grégoire, J., Hegele, R.A., Couture, P., Mancini, G.B., McPherson, R., Francis, G.A., Poirier, P., Lau, D.C., Grover, S., Genest Jr., J., Carpentier, A.C., Dufour, R., Gupta, M., Ward, R., Leiter, L.A., Lonn, E., Ng, D.S., Pearson, G.J., Yates, G.M., Stone, J.A. and Ur, E. (2013) 2012 Update of the Canadian Cardiovascular Society Guidelines for the Diagnosis and Treatment of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Canadian Journal of Cardiology, 29, 151-167.
http://dx.doi.org/10.1016/j.cjca.2012.11.032
[29] Olmetti, F., Pinna, G.D., Maestri, R., D’Armini, A., Pellgrinni, C., Vigano, M. and Lilleri, D. (2011) Heart Rate and Cardiac Allograft Vasculopathy in Heart Transplant Recipients. The Journal of Heart and Lung Transplantation, 30, 1368-1373.
http://dx.doi.org/10.1016/j.healun.2011.07.009
[30] Sander, M. and Victor, R.G. (1995) Hypertension after Cardiac Transplantation: Pathophysiology and Management. Current Opinion in Nephrology and Hypertension, 4, 443-451.
[31] Sanchez-Lazaro, I.J., Martinez-Dolz, L., Almenar-Bonet, L., Moro-Lopez, J.A., Aguero, J., Ortiz-Martinez, V., Izquierdo, M.T. and Salvador, A. (2008) Predictor Factors for the Development of Arterial Hypertension Following Heart Transplantation. Clinical Transplantation, 22, 760-764.
http://dx.doi.org/10.1111/j.1399-0012.2008.00875
[32] Radermacher, J.R., Meiners, M., Bramlage, C., Kliena, V. and Behrend, M. (1998) Pronounced Renal Vasoconstriction and Systemic Hypertension in Renal Transplant Patients Treated with Cyclosporin A versus Tacrolimus. Transplantation, 11, 3-10.
http://dx.doi.org/10.1111/j.1432-2277.1998.tb00948.x
[33] Taylor, D.O., Barr, M.L., Radovancevic, B., Renlund, D.G. and Mentzer, R.M. (1999) Randomized Control Trial Comparing Tacrolimus and Cyclosporine A in Cardiac Transplant Recipients. The Journal of Heart and Lung Transplantation, 18, 336-345.
http://dx.doi.org/10.1016/S1053-2498(98)00060-6
[34] Brozena, S.C., Johnson, M.R., Ventura, H., Hobbs, R., Miller, L., Olivari, M.T. and Clemson, B. (1996) Effectiveness and Safety of Diltiazem or Lisinopril in Treatment of Hypertension after heart Transplantation. Journal of the American College of Cardiology, 27, 1701-1712.
http://dx.doi.org/10.1016/0735-1097(96)00057-5
[35] Leenen, F.H.H., Coletta, E. and Davies, R.A. (2007) Prevention of Renal Dysfucntion and Hypertension by Amlodipine after Heart Transplant. American Journal of Cardiology, 100, 531-535.
http://dx.doi.org/10.1016/j.amjcard.2007.03.058
[36] Opie, L.H., Haus, M., Commerfod, P.J., Levetan, B., Moore, K. and Brink, J. (2002) Antihypertensive Effects of Angiotensin Converting Enzyme Inhibition by Lisinopril in Post-Transplant Patients. American Journal of Hypertension, 15, 911-916.
http://dx.doi.org/10.1016/S0895-7061(02)02992-8
[37] White, M., Ross, H., Levesque, S., Whittom, L., Pelletier, G.B., Racine, N., Meloche, S. and Voisin, L. (2009) Effects of Angiotensin-Converting Enzyme Inhibitors versus Valsartan on Cellular Signaling Events in Heart Transplant. Annals of Pharmacotherapy, 43, 831-839.
http://dx.doi.org/10.1345/aph.1L602
[38] Schroeder, J.S., Gao, S.Z., Alderman, E.L., Hunt, S.A., Johnstone, I., Boothroyd, D.B., Wiederhold, M.A. and Stinson, E.B. (1993) A Preliminary Study of Diltiazem in the Prevention of Coronary Artery Disease in Heart-Transplant Recipients. The New England Journal of Medicine, 328, 164-170.
http://dx.doi.org/10.1056/NEJM199301213280303
[39] Rudas, L., Pflugfeider, P.W., McKenzie, N., Menkins, A.H., Novick, R.J. and Kostuk, W.J. (1990) Serial Evaluation of Lipid Profiles and Risk Factors for Development of Hyperlipidemia after Cardiac Transplantation. American Journal of Cardiology, 66, 1135-1136.
http://dx.doi.org/10.1016/0002-9149(90)90518-6
[40] Zakliczynaki, M., Bogualaweka, J., Wojniak, E., Zakliczyneka, H., Ciesla, D. and Nozynski, J. (2011) In the Era of Universal Use of Statins Dyslipidemia’s Are Still Common in Heart Transplant Recipients: A Cross-Sectional Study. Transplantation Proceedings, 43, 3071-3073.
http://dx.doi.org/10.1016/j.transproceed.2011.08.052
[41] Magnani, G., Carinci, V., Magelli, C., Potena, L., Reggiani, L.B. and Branzi, A. (2000) Role of Statins in the Management of Dyslipidemia after Cardiac Transplant: Randomized Controlled Trial Comparing the Efficacy and the Safety of Atorvastatin with Pravastatin. The Journal of Heart and Lung Transplantation, 19, 710-715.
http://dx.doi.org/10.1016/S1053-2498(00)00128-5
[42] Grigioni, F., Carigi, S., Potena, L., Fabbri, F., Russo, A., Musuraca, A.C., Coccolo, F. and Magnani, G. (2006) Long-Term Safety and Effectiveness of Statins for Heart Transplant Recipients in Routine Clinical Practice. Transplantation Proceedings, 38, 1507-1510.
http://dx.doi.org/10.1016/j.transproceed.2006.02.071
[43] Manipisitkul, W., McCann, E., Lee, S. and Weir, M.R. (2009) Drug Interactions in Transplant Patients: What Everyone Should Know. Current Opinion in Nephrology and Hypertension, 18, 404-411.
http://dx.doi.org/10.1097/MNH.0b013e32832edcb2
[44] Mignat, C. (1997) Clinically Significant Drug Interactions with New Immunosuppressive Agents. Drug Safety, 16, 267-278.
http://dx.doi.org/10.2165/00002018-199716040-00004
[45] Wu, A.H., Ballantyne, C.M., Short, B.C., Torre-Amione, G., Young, J.B. and Ventura, H.O. (2005) Statin Use and Risks of Death or Fatal Rejection in the Heart Transplant Lipid Registry. American Journal of Cardiology, 95, 367-372.
http://dx.doi.org/10.1016/j.amjcard.2004.09.035
[46] Bergman, E., Lundahl, A., Fridblom, P., Hedeland, M. and Bondesson, U. (2009) Enterohepatic Disposition of Rosuvastatin in Pigs and the Impact of Concomitant Dosing with Cyclosporine and Gemfibrozil. American Society for Pharmacology and Experimental Therapeutics, 37, 2349-2358.
http://dx.doi.org/10.1124/dmd.109.029363
[47] Lemahieu, W.P.D., Hermann, M., Asberg, A., Verbeke, K., Holdaas, H., Vanrenterghem, Y. and Maes, B.D. (2005) Combined Therapy with Atorvastatin and Calcineurin Inhibitors: No Interactions with Tacrolimus. American Journal of Transplantation, 5, 2236-2243.
http://dx.doi.org/10.1111/j.1600-6143.2005.01005.x
[48] Crespo-Leiro, M.G., Paniagua, M.J., Marzoa, R., Grille, Z., Naya, C., Flores, X. and Rodriguez, J.A. (2008) The Efficacy and Safety of Ezetimibe for Treatment of Dyslipidemia after Heart Transplantation. Transplantation Proceedings, 40, 3060-3062.
http://dx.doi.org/10.1016/j.transproceed.2008.09.007
[49] Thiebald, D., Krieg, M.A., Gillard-Berguer, D., Jacquet, A.F., Goy, J.J. and Burckhardt, P. (1996) Cyclosporine Induces High Bone Turnover and May Contribute to Bone Loss after Heart Transplantation. European Journal of Clinical Investigation, 26, 549-55.
http://dx.doi.org/10.1046/j.1365-2362.1996.00170.x
[50] Cohen, A., Addonizio, L.J., Lamour, J.M., Addesso, V., Staron, R.B., Goa, P. and Shane, E. (2005) Osteoporosis in Adult Survivors of Adolescent Cardiac Transplantation May Be Related to Hyperparathyroidism, Mild Renal Insufficiency and Increased Bone Turnover. The Journal of Heart and Lung Transplantation, 24, 696-702.
http://dx.doi.org/10.1016/j.healun.2004.03.020
[51] Pisani, B. and Mullen, M. (2002) Prevention of Osteoporosis in Cardiac Transplant Recipients. Current Opinion in Cardiology, 17, 160-164.
http://dx.doi.org/10.1097/00001573-200203000-00006
[52] Homik, J., Cranney, A., Shea, B., Tugwell, P., Wells, G.A., Adachi, J. and Suarez-Almazor, M.E. (2000) Bisphosphonates for Steroid Induced Osteoporosis. The Cochrane Database of Systematic Reviews, 2, Article ID: CD001347.
[53] Kapetanakis, E.I., Antonpoulos, A.S., Antoniou, T.A., Theodoraki, K.A., Zarkallas, D. and Sfirakas, P.D. (2005) Effect of Long-Term Calcitonin Administration on Steroid-Induced Osteoporosis after Cardiac Transplantation. The Journal of Heart and Lung Transplantation, 24, 526-532.
http://dx.doi.org/10.1016/j.healun.2004.02.016
[54] Braith, R.W., Magyari, P.M., Fulton, M.N., Lisor, C.F., Vogel, S.E., Hill, J.A. and Aranda, J.M. (2006) Comparison of Calcitonin versus Calcitonin and Resistance Exercise as Prophylaxis for Osteoporosis in Heart Transplant Recipients. Transplantation, 81, 1191-1195.
http://dx.doi.org/10.1097/01.tp.0000176927.43937.bb

  
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